The predictive value of modified soluble urokinase plasminogen activator receptor (suPAR) with National Early Warning Score (NEWS) for mortality in emergency elderly patients in Japan: a prospective pilot study.

Aim: The aim of this study is to evaluate the ability of soluble urokinase plasminogen activator receptor (suPAR) and modified suPAR with National Early Warning Score (NEWS) for detecting mortality in elderly emergency patients who are older than 70 years. Methods: This is a secondary analysis of our previous study, which was a single-center prospective pilot study, carried out for 21 months in the emergency department of a secondary emergency institution in Japan. This study was carried out between September 16, 2020, and June 21, 2022. The study included all patients without trauma aged 70 years or older who presented to the emergency department. Discrimination was assessed by plotting the receiver-operating characteristic curve and calculating the area under the receiver-operating characteristic curve (AUC). Results: During the study period, 47 eligible older patients were included, among which 8 (17.0%) patients died. The median suPAR was significantly lower in the survivor's group than in the nonsurvivor's group (P < 0.01). For suPAR, the AUC for the prediction of mortality was 0.805 (95% confidence interval 0.633-0.949, P < 0.001). The AUC of modified suPAR with NEWS for mortality was higher than that of suPAR [0.865 (95% confidence interval 0.747-0.958, P < 0.001)]. Conclusion: Our single-center study has demonstrated the high utility of modified suPAR with NEWS as a predictive tool of mortality in elderly emergency patients. Evidence from multicenter studies is needed for introducing modified suPAR with NEWS in the emergency department setting.

Ability of combined soluble urokinase plasminogen activator receptor to predict preventable emergency attendance in older patients in Japan: a prospective pilot study.

Soluble urokinase plasminogen activator receptor (suPAR) is a strong and nonspecific inflammatory biomarker that reflects various immunologic reactions, organ damage, and risk of mortality in the general population. Although prior research in acute medical patients showed that an elevation in suPAR is related to intensive care unit admission and risk of readmission and mortality, no studies have focused on the predictive value of suPAR for preventable emergency attendance (PEA). This study aims to evaluate the predictive value of suPAR, which consists of a combination of white blood cell count (WBC), C-reactive protein (CRP), and the National Early Warning Score (NEWS), for PEA in older patients (>65 years) without trauma who presented to the emergency department (ED). This single-center prospective pilot study was conducted in the ED of the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Hachiouji City, Tokyo, Japan, from September 16, 2020, to June 21, 2022. The study included all patients without trauma aged 65 years or older who were living in their home or a facility and presented to the ED when medical professionals decided an emergency consultation was required. Discrimination was assessed by plotting the receiver-operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC). During the study period, 49 eligible older patients were included, and thirteen (26.5%) PEA cases were detected. The median suPAR was significantly lower in the PEA group than in the non-PEA group (p < 0.05). For suPAR, the AUC for the prediction of PEA was 0.678 (95% CI 0.499-0.842, p < 0.05), and there was no significant difference from other variables as follows: 0.801 (95% CI 0.673-0.906, p < 0.001) for WBC, 0.833 (95% CI 0.717-0.934, p < 0.001) for CRP, and 0.693 (95% CI 0.495-0.862, p < 0.05) for NEWS. Furthermore, the AUC for predicting PEA was 0.867 (95% CI 0.741-0.959, p < 0.001) for suPAR + WBC + CRP + NEWS, which was significantly higher than that of the original suPAR (p < 0.01). The cutoff values, sensitivity, specificity, and odds ratio of suPAR and suPAR + WBC + CRP + NEWS were 7.5 and 22.88, 80.6% and 83.3%, 53.8% and 76.9%, and 4.83 and 16.67, respectively. This study has several limitations. First, this was pilot study, and we included a small number of older patients. Second, the COVID-19 pandemic occurred during the study period, so that there may be selection bias in the study population. Third, our hospital is a secondary emergency medical institution, and as such, we did not treat very fatal cases, which could be another cause of selection bias. Our single-center study has demonstrated the moderate utility of the combined suPAR as a triage tool for predicting PEA in older patients without trauma receiving home medical care. Before introducing suPAR to the prehospital setting, evidence from multicenter studies is needed.

The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: a prospective study in Japan.

The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospital's workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study. We calculated the anti-SARS-CoV-2 spike-specific antibody titter (1) before vaccination, (2) 7 to 20 days after the first vaccination, and (3) A total of 7 to 20 days after the second vaccination. The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. A total of 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3,476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor exercises was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group. In the multivariate logistic regression analysis, older than 60 years, the past history of hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Again, our single-center study demonstrates that older than 60 years, hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.

Comparison of the Diagnostic Value of Immunochromatography Kits in Corona Virus Disease 2019 Patients: A Prospective Pilot Study.

INTRODUCTION: The spread of coronavirus 2019 (COVID-19) is a serious problem all over the world. Several immunochromatography kits of the antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but it is still unclear which kits have high diagnostic value. This study aims to evaluate the accuracy rate for antibody detection of each immunochromatography kit and reveal which kit has a high diagnostic value for antibody detection. METHODS: This study was carried out between 1 August 2020 and 14 October 2020 at the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital. Patients diagnosed with COVID-19 and approximately 30 days after symptom onset were included as the positive group. The serum SARS-CoV-2 antibodies were analysed using seven immunochromatography kits. RESULTS: Twenty samples (Positive group: 10 patients, Negative group: 10 healthy medical workers) were included in this study. The median age of the patients was 44 years, and the median duration from symptom onset was 30.5 days in the positive group. The accuracy rates for IgM/IgG detection were: 90.0%/100% in Kit A; 50.0%/95.0% in Kit B; 55.0%/65.0% in Kit C; 60.0%/55.0% in Kit D; 50.0%/80.0% in Kit E; 80.0%/90.0% in Kit F; and 90.0%/100% in Kit G. CONCLUSIONS: Our study showed that there is a variation of accuracy rates between immunochromatography kits for antibodies of SARS-CoV-2. COVID-19 IgG/IgM RAPID TEST CASSETTE (Hangzhou Biotest Biotech Co., Ltd., China) and Nadal COVID-19 IgG/IgM Rapid Test (BioServUK Ltd., UK: United Kingdom) have high accuracy rates for both IgM and IgG detection. Evidence from large population studies of immunochromatography kits is needed to clarify the details of diagnostic value for SARS-CoV-2.

Tenascin-C-derived peptide TNIIIA2 highly enhances cell survival and platelet-derived growth factor (PDGF)-dependent cell proliferation through potentiated and sustained activation of integrin α5ß1.

Tenascin-C is an adhesion modulatory matrix protein that is highly expressed in tumors; however, its biochemical activity involved in tumorigenesis is not fully understood. On the other hand, increasing evidence indicates the importance of integrin α5ß1 in cancer development. We previously demonstrated that tenascin-C harbors a functional site that can be released as a proadhesive peptide such as TNIIIA2. Peptide TNIIIA2 is capable of inducing activation of ß1-integrins including α5ß1 via syndecan-4. In this study the proadhesive effect of TNIIIA2 was characterized by potentiated and sustained activation of integrin α5ß1. Based on this effect, TNIIIA2 rendered nontransformed fibroblasts (NIH3T3) resistant to serum deprivation-elicited anoikis through activation of the Akt/Bcl-2 pathway. Moreover, TNIIIA2 hyperstimulated PDGF-dependent proliferation of NIH3T3 by activating integrin α5ß1. Tenascin-C, a parental protein of TNIIIA2, also stimulated PDGF-dependent proliferation, which was blocked by a matrix metalloproteinase-2/9 inhibitor and an anti-TNIIIA2 function-blocking antibody, suggesting proteolytic exposure of the proadhesive effect of TNIIIA2. Mechanistic analyses revealed that TNIIIA2 induced a lateral association of PDGF receptor ß with the molecular complex of activated integrin α5ß1 and syndecan-4 in the membrane microdomains enriched with cholesterol/caveolin-1, resulting in prolonged activation of PDGF receptor ß and the subsequent Ras/mitogen-activated protein kinase pathway in a PDGF-dependent manner. Of note, TNIIIA2 induced continuous proliferation in NIH3T3 in an integrin α5ß1-dependent manner even after they formed a confluent monolayer. Thus, it was proposed that tenascin-C might be involved in deregulated cell growth through potentiated and sustained activation of integrin α5ß1 after exposure of the proadhesive effect of TNIIIA2.

A survival case of acute mitral regurgitation and cardiogenic shock caused by subtotal occlusion of the first diagonal branch.

An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST elevation in I, aVL, V5 and V6, suggesting myocardial infarction in the lateral area of the left ventricle. A chest roentgenogram showed right pulmonary edema without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed severe mitral regurgitation and a flailing anterior mitral valve leaflet, suggesting a ruptured papillary muscle. The patient was initially treated with high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping was initiated after the patient's condition stabilized. She underwent emergency mitral valve replacement with a prosthetic valve. Complete rupture of the anterior papillary muscle was confirmed. Histological examination revealed necrosis of the anterior papillary muscle with inflammatory changes. She recovered uneventfully. Postoperative coronary angiography demonstrated subtotal occlusion of the first diagonal branch, and left ventriculography demonstrated akinesis of the lateral segment. This was a rare case in which subtotal occlusion of the first diagonal branch caused rupture of an anterior papillary muscle leading to severe mitral regurgitation.